Title
Comparison of Structure Determination Methods for Intrinsically Disordered Amyloid-β Peptides
Document Type
Article
Publication Date
2014
Published In
The Journal of Physical Chemistry B
Volume
118
Issue
24
Pages
6405-6416
DOI
10.1021/jp410275y
Recommended Citation
K. Aurelia Ball, David E. Wemmer, Teresa Head-Gordon. Comparison of Structure Determination Methods for Intrinsically Disordered Amyloid-β Peptides. The Journal of Physical Chemistry B, 2014; 118:6405-6416.
Abstract
Intrinsically disordered proteins (IDPs) represent a new frontier in structural biology since the primary characteristic of IDPs is that structures need to be characterized as diverse ensembles of conformational substates. We compare two general but very different ways of combining NMR spectroscopy with theoretical methods to derive structural ensembles for the disease IDPs amyloid-β 1–40 and amyloid-β 1–42, which are associated with Alzheimer’s Disease. We analyze the performance of de novo molecular dynamics and knowledge-based approaches for generating structural ensembles by assessing their ability to reproduce a range of NMR experimental observables. In addition to the comparison of computational methods, we also evaluate the relative value of different types of NMR data for refining or validating the IDP structural ensembles for these important disease peptides.